We propose studies in dogs to determine the roles of collateral myocardial blood flow (MBF) in the (1) deivery AND (2) actions of 14C-lidocaine and 14C-propanolol in ischemic myocardium. In order to improve understanding of the differential effects of drugs on ischemic versus normal myocardium, we will quantitate the relationships between local myocardial 14C-drug concentrations and local drug responses. A third objective is to determine whether interventions which change collateral MBF (nitroglycerin, or adenosine-" coronary steal") and, hence, the severity of ischemia, cause primary effects on drug responsivity of ischemic myocardium or whether changes in collateral MBF and, hence, drug delivery, merely cause secondary effects due to changes in 14C-drug concentrations. In addition, we plan to define the electrophysiologic and contractile responses to the 14C-drug as a function of the mass of the left ventricular myocardium whiich is ischemic and at the risk of infarction. Using anesthetized, open-chest dogs with coronary occlusions, and accurate identification of the ischemic region by a special technique, we will correlate collateral MBF (radioactive microspheres) with blood and muocardial concentrations of the 14C-drugs, arrhythmias, hemodynamics, local electrograms for ST deviation and intraventricular conduction, and segmental contraction and relaxation (by a sonomicrometer system). The integration of information regarding coronary blood flow, ventricular mechanics, electrophysiology, and pharmacodynamics should provide a broad perspective to understand the pathophysiology and pharmacotherapy of ischemic heart disease. A more comprehensive understanding of the interactions among these mechanisms might improve use of drugs to prevent angina, arrhythmias and sudden death.